The failure of injured axons to regenerate underlies the loss of functional recovery in disease states such as paraplegia and cerebral infarction. The potential for regeneration of mammalian central neural tissue exists; however, mechanisms which initiate and sustain the repair process have not been defined. This proposal is aimed at defining events associated with the anabolic response of nerve cell bodies in the superior cervical ganglion and intermediolateral nucleus of the spinal cord to axonal injury. Particular attention will be focused on the effect of axotomy on low molecular weight constituents such as oxidized and reduced pyridine nucleotides, glutathione and cyclic nucleotides, which have been implicated in regulating metabolism. Changes in these intermediates will be temporally correlated with increases in the activity of 6-phosphogluconate dehydrogenase, an enzyme associated with the formation of biosynthetic precursors, necessary for axonal growth, and lipid during the early stages of the retrograde response. Studies aimed at defining mechanisms regenerating 6-phosphogluconate dehydrogenase and at characterizing alterations in lipid that occur in axotomized nerve cell bodies of the rat superior cervical ganglion will be conducted in vivo and in organ culture. Emphasis will be placed on exploring possible alterations in glycolipids and glycoproteins, which have been associated with altered patterns of growth in other mammalian tissues. Correlation of changes in selected substrates and enzyme activities in nerve cell bodies with the loss and reestablishment of functional synapses at an appropriate end organ will be made using the model of axotomized intermediolateral nucleus neurons. Finally, the participation of axonal degeneration products in initiating and sustaining biochemical changes in injured nerve cell bodies will be evaluated in hibernating ground squirrels, a species in which transected peripheral axons survive for extended periods of time.